Synthesis and crystal structure study of diethyl aryl(benzo[d]thiazol-2- ylamino)methyl phosphonates

Article abstract of DOI:10.1002/hc.21063

A three-component synthesis of α-aminophosphonate is described from a reaction between aldehydes, 2-aminobenzothiazole, and triethyl phosphite in the presence of InCl₃ as a catalyst under solvent-free conditions for the generation of the particular α-aminophosphonates. These products have two potentially biologically active parts, aminophosphonate and benzothiazole. This method offers advantages such as short reaction times, good yields, solvent-free conditions, and easy workup with the green aspects by avoiding toxic catalysts and solvents. The crystal structure of 4b has been determined by X-ray crystallography. This compound crystallizes in the monoclinic space group C2/c with cell parameters a = 21.9285(5) A, b = 10.3221(2) A, c = 18.5979(5) A, β = 108.759(3)°, V = 3985.99(18) A³, D_calc = 1.301 mg m^-3, and Z = 8. The final R value is 0.0501 for 3741 reflections.

Full text of DOI:10.1002/hc.21063

Heteroatom Chemistry
Volume 24, Number 1, 2013
Synthesis and Crystal Structure Study of
Diethyl Aryl(benzo[d]thiazol-2-ylamino)methyl
Phosphonates
Mojtaba Lashkari,1 Nourallah Hazeri,1 Malek Taher Maghsoodlou,1
Sayyed Mostafa Habibi Khorassani,1 Niloufar Akbarzadeh Torbati,1
Asghar Hosseinian,2 Santiago Garc´ıa-Granda,3
and Laura Torre-Ferna´ndez3
1Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, P. O. Box
98135-674 Zahedan, Iran
2Department of Chemistry, College of Sciences, Hormozgan University, Bandar Abbas, Iran
3Department of Physical and Analytical Chemistry, University of Oviedo-CINN, Oviedo, Spain
Received 3 August 2012; revised 20 October 2012
INTRODUCTION
ABSTRACT: A three-component synthesis of α-
aminophosphonate is described from a reaction be-
tween aldehydes, 2-aminobenzothiazole, and triethyl
phosphite in the presence of InCl3 as a catalyst under
solvent-free conditions for the generation of the par-
ticular α-aminophosphonates. These products have
two potentially biologically active parts, aminophos-
phonate and benzothiazole. This method offers ad-
vantages such as short reaction times, good yields,
solvent-free conditions, and easy workup with the
green aspects by avoiding toxic catalysts and solvents.
The crystal structure of 4b has been determined by
X-ray crystallography. This compound crystallizes in
the monoclinic space group C2/c with cell parameters
α-Aminophosphonate is a biologically important
compound as peptidomimetics, haptens design
in antibody generation [1], and also in en-
zyme inhibitory activity [2]. In addition, α-
aminophosphonate derivatives have broad appli-
cations such as herbicids, insecticides, fungicides,
antibiotics, and pharmacological agents [3]. Among
the number of synthetic approaches regarding α-
aminophosphonates, one of the most powerful meth-
ods is the Kabachnik–Fields reaction in which alde-
hyde, amine, and di- or trialkyl phosphite are re-
acted in a one-pot setup [4]. This reaction can be
promoted by several acid catalysts such as NbCl5
[5], ChCl·2ZnCl2 [6], InCl3 [7], YbCl3 [8], Ce(OTf)4
[9], Sn(OTf)2 [10], Mg(ClO4)2 [11], LiClO4 [12],
ZrOCl2·8H2O [13], CAN [14], Yb(PFO)3 [15], SmI2
[16], TaCl5-SiO2 [17], SbCl3/Al2O [18], sulfamic acid
[19], oxalic acid [20], and silica sulfuric acid [21].
In recent years, α-aminophosphonates were synthe-
sized containing the benzothiazole moiety, which
has antitumor and antimicrobial activity [11,13,22].
Molecules featuring of the benzothiazole struc-
tural motif play a key part in a wide variety of chem-
istry. Their diverse functions range from electron
˚
˚
˚
a = 21.9285(5) A, b = 10.3221(2) A, c = 18.5979(5) A,
◦
3
˚
β = 108.759(3) , V = 3985.99(18) A , Dcalc = 1.301 mg
m
−3, and Z = 8. The final R value is 0.0501 for 3741 re-
ꢀC
flections. 2012 Wiley Periodicals, Inc. Heteroatom
Chem. 24:58–65, 2013; View this article online at wi-
leyonlinelibrary.com. DOI 10.1002/hc.21063
Correspondence to: N. Hazeri; e-mail: n_hazeri@yahoo.com.
2012 Wiley Periodicals, Inc.
ꢀC
58

Synthesis and Crystal Structure Study of Diethyl Aryl(benzo[d]thiazol-2-ylamino)methyl Phosphonates 59
Ar
NH
4a–j
O
N
S
O
EtO
OEt
P
N
S
InCl3
P
+
NH2
+
OEt
OEt
Ar
H
OEt
Solvent-free, 110°C
1
2
3
SCHEME 1 Synthesis of α-aminophosphonates 4a-j catalyzed by InCl3.
TABLE 1 Optimization of Catalyst on a Model Reactiona TABLE 2 Optimization of Reaction Conditionsa
Entry
Catalyst
Isolated Yield (%)
Catalyst
(mol%)
Temperature
(◦C)
Time
(min)
Isolated Yield
(%)
Entry
1
2
3
4
5
6
7
–
33
55
21
57
41
65
37
p-TsOH·H2O
1
2
3
4
5
6
7
8
5
10
15
5
10
15
10
15
90
90
90
100
100
100
110
110
30
30
30
30
15
13
11
11
40
56
54
45
67
67
77
70
ZrCl4
ZrOCl2·8H2O
Zr(NO3)4
InCl3
CAN
aReaction conditions: 2-Aminobenzothiazole (1.0 mmol), 4-
chlorobenzaldehyde (1.0 mmol), and triethyl phosphite (1.0 mmol)
with 10 mol% catalyst for 30 min at 100◦C under solvent-free condi-
tions.
aReaction conditions: 2-Aminobenzothiazole (1.0 mmol), 4-
chlorobenzaldehyde (1.0 mmol), triethyl phosphite (1.0 mmol), and
InCl3 as a catalyst.
transfer facilitation in the firefly luciferine cycle [23],
through antitumor [24] and antidiabetic activity [25]
to an Alzheimer disease tracer [26] and an anti-
cancer agent in pharmaceutical chemistry [27]. The
2-aminobenzothiazole nuclei, as a privileged scaf-
fold, are found in many natural products and phar-
maceuticals that exhibit remarkable biological ac-
tivities [28]. In addition, some compounds with this
skeleton have application in drugs for the treatment
of various diseases [29].
P(OEt)3
InCl3
3
N
S
O
Ar
N
S
+
NH2
N
Ar
H
–H2O
InCl3
1
2
A
O
H2
OH
EtO
EtO
O
Et
Ar
O
EtO
P
EtO
P
N
N
Ar
N
N
H
–EtOH
S
RESULTS AND DISCUSSION
S
H
4
In continuation of our ongoing research [30–36], we
investigated the InCl3-catalyzed three-component
reaction between 2-aminobenzothiazole and alde-
hydes in the presence of triethyl phosphite un-
der solvent-free and thermal conditions for the
synthesis of different α-aminophosphonates 4a–j
(Scheme 1).
At the outset of experiment, the one-
pot, three-component reaction between 2-
aminobenzothiazole, 4-chlorobenzaldehyde, and
triethyl phosphite was chosen as a pattern to opti-
mize the reaction conditions in the presence of some
catalysts such as p-TsOH·H2O, ZrCl4, ZrOCl2·8H2O,
Zr(NO3)4, InCl3, and CAN. In the absence of catalyst,
only 33% of product could be obtained when the
mixture of the reaction was heated at 100◦C for
30 min. This indicated that the catalyst should be
necessary for this transformation (Table 1). The
effect of amount of catalyst was also investigated
along with effects of temperature and time on the
B
SCHEME 2 Speculative mechanism for the synthesis of α-
aminophosphonates 4a–j catalyzed by InCl3.
yield. Herein, a reaction occurred efficiently to
afford the corresponding α-aminophosphonates in
77% yield when 10 mol% InCl3 was used at 110◦C
under solvent-free conditions (Table 2, entry 7).
A speculative mechanism is presented for the
synthesis of compounds 4a–j in Scheme 2. In the
first step, it is believed to involve the formation of
activated imine A [37]. In the second step, phosphite
adds to the C N bond of the transient imine A to af-
ford phosphonium intermediate B, which then un-
dergoes the reaction with water generated during
formation of imine to give α-amino phosphonates 4
and EtOH.
The chemical structures of all the new com-
pounds (Table 3) were confirmed by IR, 1H, 13C, and
Heteroatom Chemistry DOI 10.1002/hc

60 Lashkari et al.
TABLE 3 Synthesis of α-Aminophosphonates 4a–j.
TABLE 4 Hydrogen Bond Geometries of Compound 4b in
˚
the Crystal Packing (A, deg)
Entry
Ar
Product Time (min) Yield (%)
D
H···A
D
H
H···A
D···A
D
H···A
108
1
2
3
4
5
6
7
8
9
Ph
4-MeC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
4a
4b
4c
4d
4e
4f
14
13
11
12
12
10
13
16
16
14
77
75
77
76
70
72
71
80
89
78
N5 H5···O2
0.86 2.64
0.97 2.78
0.96 2.83
0.97 2.74
0.97 2.74
0.97 2.47
0.97 2.47
0.98 2.48
0.93 2.77
0.86 2.17
0.93 2.86
0.96 2.88
0.93 2.80
3.025 (3)
3.164 (3)
3.527 (4)
3.142 (7)
3.142 (7)
2.978 (6)
2.978 (6)
2.810 (3)
2.984 (4)
2.841 (2)
3.702 (3)
3.631 (4)
3.699 (3)
3.610 (10)
3.390 (3)
3.359 (3)
C8 H8A···O2
104
131
106
106
113
113
99
C9 H9C···N5
C10A H10A···O2
C10A H10A···O2
C10B H10D···O2
C10B H10D···O2
C12 H12···N6
C25 H25···N5
N5 H5···O2i
3-BrC6H4
3-MeOC6H4
4-HOC6H4
4-HO-3-MeOC6H3
5-Br-2-HOC6H3
4g
4h
4i
94
10
4j
135
151
136
163
135
136
145
C25 H25···O2i
C9 H9A···N6ii
C21 H21···O4iii
C11B H11E···N6iii 0.96 2.86
C21 H21···O3iii
0.93 2.66
0.93 2.55
C16 H16···O3iv
Symmetry codes: (i) –x, –y, –z; (ii) –x, y, –z –1/2; (iii) –x, –y + 1, –z;
(iv) x –1/2, –y +1/2, z – 1/2.
FIGURE 1 ORTEP view of the molecular geometry of com-
pound 4b. Ellipsoids have been drawn at the 50% probability
level.
31P NMR spectroscopy, elemental analysis, and mass
spectrometry. The structure of compound 4b estab-
lished through single-crystal X-ray analysis (Fig. 1).
Compound 4b exhibited characteristic IR stretch-
ing frequencies at 3234 and 1232 cm−1 for N H
and P O, respectively [38]. In the 1H NMR spec-
trum of 4b, the P C H proton resonated as a dou-
FIGURE 2 A pair of hydrogen bonds in a centrosymmetric
dimer of 4b.
(3JCP), respectively [38, 40, 41]. The 31P NMR signal
appeared at δ 20.90 for 4b [42].
In this compound, there are weak intermolecu-
lar P O···H N hydrogen bond (Table 4) that are
effective in the stabilization of the crystal structure.
A pair of hydrogen bond can be seen in a centrosym-
metric dimer of compound 4b (Fig. 2).
2
blet of doublet at δ 5.53 with JPH = 22.0 Hz and
3JHH = 8.4 Hz due to its coupling with phosphorus
and NH [39]. A broad singlet at δ 7.46 corresponds
to NH proton (using D2O exchange). The methylene
protons of P O CH2 CH3 showed a multiplet in
the region δ 3.76–4.22, and the methyl protons of
P OCH2 CH3 gave two triplets at δ 1.18 and 1.31
with 3JHH = 6.8 Hz [39].
CONCLUSIONS
The carbon chemical shifts were observed in the
title compounds for P CH, P O CH2 (two δ), and
P O C CH3 (two δ) at δ 55.46, 63.50, 63.65, 16.27,
and 16.50, respectively with coupling constants in-
volving 154.9 Hz (1JCP), 7.0 Hz (2JCP), and 6.0 Hz
In conclusion, we have developed
a simple
and convenient method for the synthesis of α-
aminophosphonates through the three-component
reaction between 2-aminobenzothiazole, aldehydes,
Heteroatom Chemistry DOI 10.1002/hc

Synthesis and Crystal Structure Study of Diethyl Aryl(benzo[d]thiazol-2-ylamino)methyl Phosphonates 61
and triethyl phosphite catalyzed by InCl3 (10 mol%)
(100), 252 (8), 251 (14), 150 (5), 105 (5); Anal. Calcd
for C19H23N2O3PS: C, 58.45; H, 5.94; N, 7.17. Found:
C, 58.63; H, 6.01; N, 7.23.
at 110◦C under solvent-free conditions. The ad-
vantages of the present method are short reaction
times, good yields, solvent-free conditions, and easy
workup with the green aspects by avoiding toxic cat-
alysts and solvents.
Diethyl (4-chlorophenyl)(benzo[d]thiazol-2-ylam-
ino)methyl Phosphonate (4c). White powder; mp
195–198◦C; IR (KBr): ν 3230 (NH), 1230 (P O) cm−1
;
1H NMR (CDCl3, 400 MHz): δH 1.17 and 1.24 (2t,
J = 6.8 Hz, 2CH3, 6H), 3.93–4.19 (m, 2CH2, 4H), 5.79
EXPERIMENTAL
(d, JHP = 21.6 Hz, CHP, 1H), 7.06–7.67 (m, Harom
,
General Procedure for Synthesis of
α-Aminophosphonates (4a-j)
8H), 8.19 (brs, NH, 1H); 13C NMR (CDCl3, 100 MHz):
δC 16.31 and 16.53 (2d, JCP = 5.0 Hz, 2CH3), 54.92
(d, JCP = 156.0 Hz, CHP), 63.72 (d, JCP = 7.0 Hz,
2CH2), 119.33 (s), 120.69 (s), 121.72 (s), 125.78 (s),
128.72 (s), 129.67 (d, JCP = 6.0 Hz), 131.16 (s), 134.03
(s), 151.92 (s), 165.68 (d, JCP = 12.0 Hz); 31P NMR
(CDCl3, 162 MHz): δP 20.35; MS (m/z) (%): 412 (M+
+ 2, 18), 410 (M+, 48), 275 (100), 273 (83), 255 (16),
237 (26), 135 (10); Anal. Calcd for C18H20ClN2O3PS:
C, 52.62; H, 4.91; N, 6.82. Found: C, 52.81; H, 4.90;
N, 6.88
To a mixture of 2-aminobenzothiazole (1.0 mmol),
aldehydes (1.0 mmol), and triethyl phosphite
(1.0 mmol), InCl3 (10 mol%) was added and stirred
at 110◦C for appropriate time (Table 3). After com-
pletion of the reaction as monitored by TLC, the mix-
ture was cooled to room temperature and the mix-
ture was washed with EtOAc (3 × 3 mL) to afford
pure α-aminophosphonates 4a–j.
Diethyl Phenyl(benzo[d]thiazol-2-ylamino)methyl
Phosphonate (4a). White powder; mp 155–157◦C;
Diethyl (3-chlorophenyl)(benzo[d]thiazol-2-ylam-
1
IR (KBr): ν 3223 (NH), 1249 (P O) cm−1; H NMR
ino)methyl Phosphonate (4d). White powder; mp
153–156◦C; IR (KBr): ν 3224 (NH), 1237 (P O) cm−1
;
(CDCl3, 400 MHz): δH 1.16 and 1.31 (2t, J = 6.8 Hz,
2CH3, 6H), 3.74–4.22 (m, 2CH2, 4H), 5.44 (dd,
JHP = 22.0 Hz, JHH = 6.4 Hz, CHP, 1H), 6.58 (brs,
NH, 1H), 7.08–7.58 (m, Harom, 9H); 13C NMR (CDCl3,
100 MHz): δC 16.26 and 16.52 (2d, JCP = 6.0 Hz,
2CH3), 55.68 (d, JCP = 153.9 Hz, CHP), 63.54 and
63.68 (2d, JCP = 7.0 Hz, 2CH2), 119.26 (s), 120.67 (s),
121.72 (s), 125.70 (s), 128.18 (d, JCP = 2.0 Hz), 128.34
(d, JCP = 6.0 Hz), 128.55 (d, JCP = 1.0 Hz), 131.20
(s), 135.29 (s), 152.07 (s), 165.96 (d, JCP = 12.0 Hz);
31P NMR (CDCl3, 162 MHz): δP 20.90; MS (m/z) (%):
376 (M+, 6), 273 (20), 255 (11), 239 (100), 237 (5),
150 (3); Anal. Calcd for C18H21N2O3PS: C, 57.44; H,
5.62; N, 7.44. Found: C, 57.69; H, 5.67; N, 7.53.
1H NMR (CDCl3, 400 MHz): δH 1.20 and 1.32 (2t,
J = 7.2 Hz, 2CH3, 6H), 3.82–4.31 (m, 2CH2, 4H), 6.00
(dd, JHP = 22.4 Hz, JHH = 6.8 Hz, CHP, 1H), 7.09–7.61
(m, Harom, 8H), 7.23 (br, NH, 1H); 13C NMR (CDCl3,
100 MHz): δC 16.27 and 16.50 (2d, JCP = 5.0 Hz,
2CH3), 55.08 (d, JCP = 154.9 Hz, CHP), 63.79 and
63.82 (2d, JCP = 4.0 Hz, 2CH2), 119.35 (s), 120.70 (s),
121.87 (s), 125.75 (s), 126.48 (d, JCP = 6.0 Hz), 128.34
(s), 128.38 (d, JCP = 6.0 Hz), 129.79 (d, JCP = 2.0 Hz),
131.24 (s), 134.44 (d, JCP = 2.0 Hz), 151.93 (s), 165.67
(d, JCP = 12.0 Hz); 31P NMR (CDCl3, 162 MHz): δP
20.31; MS (m/z) (%): 412 (M+ + 2, 3), 410 (M+, 8),
275 (44), 273 (100); Anal. Calcd for C18H20ClN2O3PS:
C, 52.62; H, 4.91; N, 6.82. Found: C, 52.78; H, 4.99;
N, 6.90.
Diethyl (4-methylphenyl)(benzo[d]thiazol-2-ylam-
ino)methyl Phosphonate (4b). Yellow powder; mp
176–178◦C; IR (KBr): ν 3234 (NH), 1232 (P O)
Diethyl (2-chlorophenyl)(benzo[d]thiazol-2-ylam-
cm−1
;
1H NMR (CDCl3, 400 MHz): δH 1.18 and
ino)methyl Phosphonate (4e). White powder; mp
1.31 (2t, J = 6.8 Hz, 2CH3, 6H), 2.34 (s, CH3, 3H),
3.76–4.22 (m, 2CH2, 4H), 5.53 (dd, JHP = 22.0 Hz,
JHH = 8.4 Hz, CHP, 1H), 7.06–7.56 (m, Harom, 8H),
7.46 (br, NH, 1H); 13C NMR (CDCl3, 100 MHz): δC
16.27 and 16.50 (2d, JCP = 6.0 Hz, 2CH3), 21.22 (s,
CH3), 55.46 (d, JCP = 154.9 Hz, CHP), 63.50 and
63.65 (2d, JCP = 7.0 Hz, 2CH2), 119.28 (s), 120.69
(s), 121.76 (s), 125.74 (s), 128.15 (d, JCP = 6.0 Hz),
129.31 (d, JCP = 2.0 Hz), 131.10 (s), 132.02 (s),
138.01 (d, JCP = 3.0 Hz), 152.02 (s), 165.93 (d,
JCP = 12.0 Hz); 31P NMR (CDCl3, 162 MHz): δP 20.90;
MS (m/z) (%): 390 (M+, 33), 281 (21), 254 (67), 253
193–195◦C; IR (KBr): ν 3219 (NH), 1247 (P O) cm−1
;
1H NMR (CDCl3, 400 MHz): δH 1.14 and 1.36 (2t,
J = 7.2 Hz, 2CH3, 6H), 3.72–4.31 (m, 2CH2, 4H),
6.00 (dd, JHP = 22.8 Hz, JHH = 6.8 Hz, CHP, 1H),
7.07–7.73 (m, Harom, NH, 9H); 13C NMR (CDCl3,
100 MHz): δC 16.18 and 16.50 (2d, JCP = 6.0 Hz,
2CH3), 52.46 (d, JCP = 155.9 Hz, CHP), 63.74 and
63.87 (2d, JCP = 7.0 Hz, 2CH2), 119.57 (s), 120.71
(s), 121.84 (s), 125.77 (s), 127.24 (d, JCP = 3.0 Hz),
129.28 (d, JCP = 4.0 Hz), 129.36 (d, JCP = 5.0 Hz),
129.56 (d, JCP = 2.0 Hz), 131.26 (s), 133.65 (s),
134.32 (d, JCP = 7.0 Hz), 152.12 (s), 165.81 (d,
Heteroatom Chemistry DOI 10.1002/hc

62 Lashkari et al.
JCP = 13.0 Hz); 31P NMR (CDCl3, 162 MHz): δP 20.21;
MS (m/z) (%): 412 (M+ + 2, 7), 410 (M+, 19), 275
(85), 273 (100), 237 (25), 84 (19); Anal. Calcd for
C18H20ClN2O3PS: C, 52.62; H, 4.91; N, 6.82. Found:
C, 52.77; H, 4.96; N, 6.85.
100 MHz): δC 16.56 and 16.73 (2d, JCP = 6.0 Hz,
2CH3), 54.20 (d, JCP = 156.0 Hz, CHP), 62.84 and
63.01 (2d, JCP = 6.0 Hz, 2CH2), 115.39 (s), 118.75
(s), 121.48 (s), 121.78 (s), 126.04 (s), 129.83 (d,
JCP = 6.0 Hz), 131.20 (s), 152.06 (s), 157.34 (s) 165.80
(d, JCP = 10.0 Hz); 31P NMR (DMSO-d6): δP 21.37; MS
(m/z) (%): 392 (M+, 4), 283 (9), 273 (19), 255 (100),
150 (8), 135 (10), 83 (11), 65 (11); Anal. Calcd for
C18H21N2O4PS: C, 55.09; H, 5.39; N, 7.14. Found: C,
55.31; H, 5.47; N, 7.19.
Diethyl (3-bromophenyl)(benzo[d]thiazol-2-ylam-
ino)methyl Phosphonate (4f). White powder; mp
159–162◦C; IR (KBr): ν 3227 (NH), 1235 (P O) cm−1
;
1H NMR (CDCl3, 400 MHz): δH 1.21 and 1.32 (2t,
J = 6.8 Hz, 2CH3, 6H), 3.86–4.31 (m, 2CH2, 4H), 5.55
(dd, JHP = 22.0 Hz, JHH = 6.4 Hz, CHP, 1H), 7.02–7.75
(m, Harom, 8H), 7.18 (br, NH, 1H); 13C NMR (CDCl3,
100 MHz): δC 16.30 and 16.53 (2d, JCP = 6.0 Hz,
2CH3), 54.94 (d, JCP = 154.9 Hz, CHP), 63.83 and
63.90 (2d, JCP = 4.0 Hz, 2CH2), 119.30 (s), 120.68
(s), 121.81 (s), 122.60 (d, JCP = 3.0 Hz) 125.71 (s),
126.98 (d, JCP = 5.0 Hz), 130.07 (d, JCP = 1.0 Hz),
131.21 (d, JCP = 2.0 Hz), 131.21 (s), 131.27 (s), 131.31
(d, JCP = 2.0 Hz) 137.96 (s), 151.94 (s), 165.75 (d,
JCP = 14.0 Hz); 31P NMR (CDCl3, 162 MHz): δP 20.38;
MS (m/z) (%): 456 (M+ + 2, 7), 454 (M+, 7), 319 (100),
317 (96), 238 (3); Anal. Calcd for C18H20BrN2O3PS:
C, 47.48; H, 4.43; N, 6.15. Found: C, 47.70.; H, 4.51;
N, 6.19.
Diethyl (4-hydroxy-3-methoxyphenyl)(benzo[d]
thiazol-2-ylamino)methyl Phosphonate (4i). White
powder; mp 206–208◦C; IR (KBr): ν 3206 (NH),
3425–3160 (br, OH), 1246 (P O) cm−1 1H NMR
;
(DMSO-d6, 400 MHz): δH 1.08 and 1.14 (2t, J =
7.2 Hz, 2CH3, 6H), 3.78 (s, OCH3, 3H), 3.86–4.06
(m, 2CH2, 4H), 5.62 (d, JHP = 20.8 Hz, CHP, 1H),
6.75–7.69 (m, Harom, 7H), 8.97 and 9.10 (2br,
OH, NH, 2H). 13C NMR (DMSO-d6, 100 MHz): δC
16.58 and 16.74 (2d, JCP = 5.0 Hz, 2CH3), 54.47
(d, JCP = 155.0 Hz, CHP), 56.14 (s, OCH3), 62.86
and 63.02 (2d, JCP = 7.0 Hz, 2CH2), 112.84 (d,
JCP = 5.0 Hz), 115.46 (s), 118.74 (s), 121.30 (d,
JCP = 6.0 Hz), 121.49 (s), 121.80 (s), 126.07 (s),
126.72 (s), 131.17 (s), 146.56 (s), 147.72 (s), 152.07
(s), 165.78 (d, JCP = 8.0 Hz); 31P NMR (DMSO-d6
162 MHz): δP 21.25; MS (m/z) (%): 422 (M+, 5), 317
(12), 285 (100), 273 (7), 178 (8), 150 (89), 123 (10),
96 (8); Anal. Calcd for C19H23N2O5PS: C, 54.02; H,
5.49; N, 6.63. Found: 54.33; H, 5.44; N, 6.70.
Diethyl (3-methoxyphenyl)(benzo[d]thiazol-2-yla-
mino)methyl Phosphonate (4g). Yellow powder; mp
138–140◦C; IR (KBr): ν 3231 (NH), 1257 (P O) cm−1
;
1H NMR (CDCl3, 400 MHz): δH 1.18 and 1.31 (2t, J =
7.2 Hz, 2CH3, 6H), 3.78 (s, OCH3, 3H), 3.80–4.30 (m,
2CH2, 4H), 5.54 (dd, JHP = 22.0 Hz, JHH = 4.00 Hz,
CHP, 1H), 6.84–7.56 (m, Harom, 8H), 7.44 (br, NH,
1H); 13C NMR (CDCl3, 100 MHz): δC 16.27 and
16.49 (2d, JCP = 6.0 Hz, 2CH3), 55.23 (s, OCH3),
55.82 (d, JCP = 153.9 Hz, CHP), 63.55 and 63.71
(2d, JCP = 7.0 Hz, 2CH2), 113.82 (d, JCP = 2.0 Hz),
119.32 (s), 120.54 (d, JCP = 6.0 Hz), 120.70 (s), 121.80
(s), 125.75 (s), 129.56 (d, JCP = 2.0 Hz), 131.14 (s),
136.64 (s), 152.03 (s), 159.72 (d, JCP = 2.0 Hz) 165.93
(d, JCP = 13.0 Hz); 31P NMR (CDCl3, 162 MHz): δP
20.71; MS (m/z) (%): 406 (M+, 7), 269 (100), 255 (19),
150 (16), 135 (8); Anal. Calcd for C19H23N2O4PS: C,
56.15; H, 5.70; N, 6.89. Found: C, 56.25; H, 5.79; N,
6.86.
Diethyl (5-bromo-2-hydroxyphenyl)(benzo[d]thi-
azol-2-ylamino)methyl Phosphonate (4j). White
powder; mp 193–195◦C; IR (KBr): ν 3220 (NH),
3420–3154 (br, OH), 1238 (P O) cm−1 1H NMR
;
(CDCl3, 400 MHz): δH 1.23 and 1.34 (2t, J = 7.2 Hz,
2CH3, 6H), 4.02–4.31 (m, 2CH2, 4H), 5.62 (d,
JHP = 24.0 Hz, CHP, 1H), 6.58 (br, NH, 1H), 6.90–
7.86 (m, Harom, NH, 8H), 10.67 (br, OH, 1H); 13C
NMR (CDCl3, 100 MHz): δC 16.20 and 16.51 (2d,
JCP = 6.0 Hz, 2CH3), 49.84 (d, JCP = 162.0 Hz, CHP),
64.10 and 64.17 (2d, JCP = 4.0 Hz, 2CH2), 112.73 (s),
118.88 (s), 121.09 (s), 121.56 (s), 125.54 (s), 126.24
(s), 130.46 (s), 131.66 (d, JCP = 5.0 Hz), 133.07 (s),
149.81 (s), 155.12 (d, JCP = 10.0 Hz), 167.14 (d,
JCP = 14.0 Hz); 31P NMR (CDCl3, 162 MHz): δP
20.90; MS (m/z) (%): 472 (M+ + 2, 16), 470 (M+,16),
426 (25), 397 (8), 335 (100), 333 (99), 317 (14), 150
(13), 135 (26); Anal. Calcd for C18H20BrN2O4PS: C,
45.87; H, 4.28; N, 5.94. Found: C, 46.11; H, 4.34; N,
6.03.
Diethyl (4-hydroxyphenyl)(benzo[d]thiazol-2-yla-
mino)methyl Phosphonate (4h). White powder; mp
215–218◦C; IR (KBr): ν 3209 (NH), 3431–3147
(br, OH), 1228 (P O) cm−1 1H NMR (DMSO-d6,
;
400 MHz): δH 1.07 and 1.14 (2t, J = 7.2 Hz, 2CH3,
6H), 3.86–4.05 (m, 2CH2, 4H), 5.53 (d, JHP = 20.8 Hz,
CHP, 1H), 6.75–7.68 (m, Harom, 8H), 8.97 and
9.55 (2br, OH, NH, 2H). 13C NMR (DMSO-d6,
Heteroatom Chemistry DOI 10.1002/hc

Synthesis and Crystal Structure Study of Diethyl Aryl(benzo[d]thiazol-2-ylamino)methyl Phosphonates 63
TABLE 5 Crystal Data and Structure Refinement for Com-
ments of 4b were made on an Oxford Diffraction
Xcalibur Gemini R CCD single crystal diffractome-
ter 120K (Cu Kα radiation, graphite monochroma-
pound 4b
Empirical formula
Formula weight
Temperature
Crystal system
Space group
C19H23N2O3PS
390.42
120(2)
Monoclinic
C2/c
˚
tor, λ = 1.54180 A). The structure of title compound
was solved by SIR2004 [43] and refined by full ma-
trix least squares on F2 (SHELXL-97) [44]. Absorp-
tion correction, data collection, cell refinement, and
data reduction have been carried out using CrysAl-
isPro [45], PARST97 [46] for the geometrical cal-
culations, ORTEP-3 for windows [47] and Mercury
[48] for molecular graphics, and WinGX (publica-
tion material) [49].
˚
Unit cell dimensions
a = 21.9285(5) A
˚
b = 10.3221(2) A
˚
c = 18.5979(5) A
β = 108.759(3)
3
˚
Volume
3985.99(18) A
Z
8
Density (calculated)
Absorption coefficient
Crystal size
θ range for data collection
Index ranges
1.301 mg m−3
2.375
0.04 × 0.11 × 0.33 mm3
CRYSTALLOGRAPHIC DATA
2.3–35.25◦
–24 ≤ h ≤ 26, –8 ≤ k ≤ 12,
–22 ≤ l ≤ 21
CCDC 888011 contains the supplementary crystal-
lographic data for this paper. These data can be
obtained free of charge from the Cambridge Crys-
tallographic Data Center. Copies of the data can be
obtained, free of qcharge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-
(0)1223–336033, e-mail: deposit@ccdc.cam.ac.uk),
or via www.ccdc.cam.ac.uk/data_request/cif
Reflections collected
Independent reflections
Goodness-of-fit on F2
Data/restraints/parameters
Final R indices [I>2σ(I)]
R indices (all data)
8067
3741 [R(int) = 0.03]
1.069
3741/4/244
R1 = 0.0501 wR2 = 0.1205
R1 = 0.0606 wR2 = 0.1290
888011
CCDC number
CRYSTAL STRUCTURE ANALYSIS
Crystallography
The single crystals were grown from a CH2Cl2/n-
Compound 4b was synthesized from the reaction be-
hexane solution. The X-ray diffraction measure-
tween 2-aminobenzothiazole, benzaldehyde, triethyl
TABLE 6 Selected Bond Lengths, Bond Angles, and Torsion Angles for Compound 4b
Bond Lengths
Bond Angles
(◦)
Torsion Angles
(◦)
˚
(A)
P1–O2
P1 –O3
P1–O4
P1–C12
O3–C8
1.4718(17)
1.5712(19)
1.5625(17)
1.823(2)
1.442(4)
1.493(5)
1.450(6)
1.427(10)
1.477(7)
1.448(11)
1.461(3)
1.360(3)
1.766(2)
1.747(2)
1.295(3)
1.392(3)
1.512(3)
C13–S7–C14
C13–N6—C19
S7–C13–N6
C12–N5—C13
P1–C12–C20
O2–P1–O3
P1–O3–C8
O3–C8–C9
O2–P1–O4
P1–O4–C10B
P1–O4–C10A
O4–C10B–C11B
O4–C10A–C11A
O2–P1–C12
O3–P1–O4
O3–P1–C12
O4–P1–C12
P1–O4–C10A
P1–C12–N5
N5–C12—C20
S7–C13–N5
N5–C13—N6
S7–C14–C19
S7 -C14 -C15
88.26(10)
109.92(19)
116.65(17)
118.15(18)
112.63(17)
115.03(10)
123.82(17)
108.8(3)
116.61(10)
118.4(3)
127.2(3)
109.5(5)
110.9(6)
112.37(10)
100.22(9)
106.91(10)
104.39(10)
127.2(3)
106.67(15)
113.48(19)
119.05(16)
124.3(2)
C14–S7–C13–N5
C14–S7–C13–N6
O2–P1–O3–C8
–178.4(2)
0.7(2)
47.0(2)
O4–P1–O3–C8
172.9(2)
–78.5(2(
–28.1(3)
–152.9(3)
–152.9(3
–48.75(18)
76.37(17)
78.35(16)
–156.53(14)
–176.02(14
–50.90(17
111.1(3)
137.7(5)
–157.40(17)
78.0(3)
–163.39(17)
17.6(3)
–1.1(3)
178.0(2)
0.9(3)
–179.4(2)
106.7(2
C12–P1–O3–C8
O2–P1–O4–C10B
O3–P1-O4–C10B
O3–P1–O4–C10B
O2-P1–C12-N5
O2–P1–C12–C20
O3–P1–C12–N5
O3–P1–C12–C20
O4–P1–C12–N5
O4–P1–C12–C20
P1–O3–C8–C9
P1–O4–C10B–C11B
C13–N5–C12–P1
C13–N5–C12–C20
C12–N5–C13–S7
C12–N5–C13–N6
C19–N6 -C13–S7
C19–N6–C13–N5
C13–N6–C19 -C14
C13–N6–C19–C18
P1–C12–C20–C21
P1–C12–C20–C25
C8–C9
O4–C10B
C10B–C11B
O4–C10A
C10A–C11A
N5–C12
N5 -C13
S7–C13
S7–C14
N6–C13
N6–C19
C12–C20
109.23(17)
128.95(19)
–74.0(3)
Heteroatom Chemistry DOI 10.1002/hc

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phosphite, and InCl3 as a catalyst. The molecular
structure of compound 4b, showing the atom num-
bering scheme is presented in Fig. 1.
Crystallographic data and the refinement proce-
dures are given in Table 5, and selected bond lengths,
bond angles, and torsion angles of 4b are listed in
Table 6. As can be seen, there is good agreement
between the crystallographic and theoretical data.
ACKNOWLEDGMENTS
We gratefully acknowledge the funding support re-
ceived for this project from the Research Council
of the University of Sistan and Baluchestan. This
work was partially supported by FEDER funding, the
Spanish Ministerio de Econom´ıa y Competitividad
MAT2006–01997 and MAT2010-15094 and the Fac-
tor´ıa de Cristalizacio´n (Consolider Ingenio 2010).
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